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| Status |
Public on Jul 01, 2020 |
| Title |
β-catenin safeguards the ground state of pluripotency by strengthening the robustness of the transcriptional apparatus [GRO-seq] |
| Organism |
Mus musculus |
| Experiment type |
Other
|
| Summary |
Mouse embryonic stem cells (ESCs) cultured with MEK and GSK3 inhibitors (2i) more closely resemble the inner cell mass of pre-implantation blastocysts than those cultured with serum/LIF (SL). The transcriptional mechanisms governing this pluripotent ground state are yet unresolved. Release of promoter-proximal paused RNA polymerase II (Pol2) is a multistep process necessary for pluripotency and cell cycle gene transcription in SL. Here, we show that β-catenin, stabilized by GSK3 inhibition in 2i, supplies transcriptional co-regulators including BRD4, CDK9, Mediator, Cohesin, and p300 at pluripotency loci. This selectively strengthens pluripotency loci and renders them addicted to transcription initiation for productive gene body elongation in detriment to Pol2 pause release. By contrast, cell cycle genes are not bound by β-catenin and, thus, proliferation/self-renewal are still tightly controlled by the Pol2 pause release mechanism under 2i conditions. Our findings help to explain how pluripotency is preserved in the ground state and also provide a general model for transcriptional resilience/adaptation upon network perturbation in other biological contexts.
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| |
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| Overall design |
GRO-seq of mouse ESCs cultured in different conditions.
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| Contributor(s) |
Lai Y |
| Citation(s) |
32832621 |
| |
| Submission date |
Nov 13, 2019 |
| Last update date |
Sep 08, 2020 |
| Contact name |
Yiwei Lai |
| E-mail(s) |
[email protected]
|
| Organization name |
Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences
|
| Department |
South China Institute for Stem Cell Biology and Regenerative Medicine Key Laboratory of Regenerative Biology, CAS
|
| Lab |
Miguel
|
| Street address |
190 Kai Yuan Avenue, Science Park
|
| City |
Guangzhou |
| State/province |
Guangdong |
| ZIP/Postal code |
510530 |
| Country |
China |
| |
|
| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE123692 |
β-catenin safeguards the ground state of pluripotency by strengthening the robustness of the transcriptional apparatus |
|
| Relations |
| BioProject |
PRJNA589310 |
| SRA |
SRP229740 |
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